title: The cytotoxic effect of α-tomatine in MCF-7 human adenocarcinoma breast cancer cells depends on its interaction with cholesterol in incubation media and does not involve apoptosis induction.
abstract: In recent years, α-tomatine has been studied for its anticancer activity. In the present study, we focused on the cytotoxic effect of α-tomatine in the MCF-7 human breast adenocarcinoma cell line, its mechanism of action, biotransformation and stability in the culture medium. We observed an inhibition of cell proliferation and viability at concentrations of 6 and 9 µM but then a recovery of cells occurred. The recovery was not caused by the biotransformation of α-tomatine in MCF-7 cells, but by a substantial decrease in the concentration of α-tomatine in the culture medium due to its binding with cholesterol. Regarding the mechanism of action of α-tomatine, we observed no DNA damage, no changes in the levels of the proteins p53 and p21(WAF1/Cip1), and no apoptosis (neither activated caspase-8 and -9, nor sub-G1 peak, or morphological signs). We found a loss of ATP in α-tomatine-treated cells. These results support the conclusion that α-tomatine does not induce apoptosis in the MCF-7 cell line.
authors.affiliation: Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Sucha
authors.forename: Milos
authors.initials: M
authors.lastname: Hroch
authors.forename: Martina
authors.initials: M
authors.lastname: Rezacova
authors.forename: Emil
authors.initials: E
authors.lastname: Rudolf
authors.forename: Radim
authors.initials: R
authors.lastname: Havelek
authors.forename: Ludek
authors.initials: L
authors.lastname: Sispera
authors.forename: Jana
authors.initials: J
authors.lastname: Cmielova
authors.forename: Renata
authors.initials: R
authors.lastname: Kohlerova
authors.forename: Ales
authors.initials: A
authors.lastname: Bezrouk
authors.forename: Pavel
authors.initials: P
authors.lastname: Tomsik
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D014053:Tomatine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; C484751:alpha-tomatine; D014053:Tomatine; D002784:Cholesterol